Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy.

The intermediate filament cytoskeleton of corneal epithelial cells is composed of cornea-specific keratins K3 and K12 (refs 1,2). Meesmann's corneal dystrophy (MCD) is an autosomal dominant disorder causing fragility of the anterior corneal epithelium, where K3 and K12 are specifically expressed. We postulated that dominant-negative mutations in these keratins might be the cause of MCD. K3 was mapped to the type-II keratin gene cluster on 12q; and K12 to the type-I keratin cluster on 17q using radiation hybrids. We obtained linkage to the K12 locus in Meesmann's original German kindred (Zmax = 7.53; theta = 0) and we also showed that the phenotype segregated with either the K12 or the K3 locus in two Northern Irish pedigrees. Heterozygous missense mutations in K3 (E509K) and in K12 (V143L; R135T) completely co-segregated with MCD in the families and were not found in 100 normal unrelated chromosomes. All mutations occur in the highly conserved keratin helix boundary motifs, where dominant mutations in other keratins have been found to severely compromise cytoskeletal function, leading to keratinocyte fragility phenotypes. Our results demonstrate for the first time the molecular basis of Meesmann's corneal dystrophy.

Ultrasonic findings after treatment of retinal detachment by intravitreal silicone instillation.

Postoperative A- and B-scan ultrasonography in 55 patients with complicated retinal detachment who had undergone pars plana vitrectomy with intravitreal silicone oil tamponade showed that the position of the retina could be demonstrated. The reproducible phenomena in eyes with clear media indicated that the same characteristics could be used for diagnosis in eyes with opacification of the lens or cornea.

Primary antiphospholipid antibody syndrome and retinal occlusive vasculopathy.

PURPOSE: To report a 31-year-old healthy patient with retinal venous occlusion in his left eye attributable to primary antiphospholipid antibody syndrome. METHODS: The patient was examined clinically. Multiple serologic and clinical investigations were performed to determine the causative disease. He was closely followed up for more than 3 years. RESULTS: The presence of lupus anticoagulant in our patient was indicated by a kaolin clotting time index of 27 (normal, <17) and confirmed by the demonstration of IgG antibodies against phospholipids. After long-term oral anticoagulant treatment for 2 years, lupus anticoagulant levels returned to normal, and therapy was stopped. No further thrombotic event occurred during follow-up. CONCLUSIONS: In retinal vascular occlusions of unexplained origin, antiphospholipid antibodies may play an important role in the pathogenesis. Detecting these antibodies in the serum of patients with retinal vascular occlusion helps determine the appropriate treatment with long-term oral anticoagulants.

Bilateral cataract after phakic posterior chamber top hat-style silicone intraocular lens.

BACKGROUND: New strategies have been developed for surgical treatment of high myopia. Recently, implantation of minus power posterior chamber intraocular lenses (IOL) into phakic eyes has been introduced. METHODS: We report a 37 year-old female patient who developed bilateral anterior subcapsular cataract 7 years after minus-power, top hat-style silicone posterior chamber IOL implantation in Russia. The corrected visual acuity was right eye 20/200 and left eye 20/63. Because of the high myopia and the posterior chamber IOL in her phakic eyes, biometry for IOL calculation gave contradictory results. Both posterior chamber IOLs were found to be adherent to the crystalline lenses. After posterior chamber IOL explantation and phacoemulsification, intraoperative retinoscopy was performed. With this aphakic refraction, the IOL power was calculated and implanted. The explanted posterior chamber IOLs were examined by scanning electron microscopy. RESULTS: After bilateral operation the corrected visual acuity increased to right eye 20/32 and left eye 20/40, respectively. On scanning electron microscopy, a membranous structure of unknown origin was noted on the entire surface of the explanted posterior chamber IOLS. CONCLUSION: There is a potential risk of cataract formation after implantation of this top hat-style silicone posterior chamber IOL. If cataract extraction in this specific situation is needed, a different approach for calculating the aphakic IOL power is necessary, such as intraoperative retinoscopy.

Microphthalmos with colobomatous orbital cyst: clinical, histological, immunohistological, and electronmicroscopic findings.

A case of unilateral microphthalmos with orbital cyst is presented. This rare and severe malformation is a non-hereditary disorder. Pathologically it represents a failure in the closure of the embryonic fissure at the 7-14 mm stage of gestation. Staining for neurofilaments permitted the identification of rudimentary optic nerve fibers within the gliomatous cyst wall. Special stains for glial fibrillary acidic protein as well as scanning and transmission electron microscopy were used to characterise the neuroglial cell lining of the cyst wall, and to show microvilli on its inner surface.

A novel keratin 12 mutation in a German kindred with Meesmann's corneal dystrophy.

AIM: To study a kindred with Meesmann's corneal dystrophy (MCD) to determine if a mutation within the cornea specific K3 or K12 genes is responsible for the disease phenotype. METHODS: Slit lamp examination of the cornea in four members of the kindred was carried out to confirm the diagnosis of MCD. The region encoding the helix initiation motif (HIM) of the K12 polypeptide was polymerase chain reaction (PCR) amplified from genomic DNA derived from affected individuals in the kindred. PCR products generated were subjected to direct automated sequencing. Restriction enzyme analysis employing Ban I was used to confirm the presence of the mutation in affected individuals of the family. RESULTS: Sequencing of the K12 gene in an affected individual from the family revealed a novel heterozygous missense mutation (413A-->C), predicting the substitution of a proline for a glutamine at codon 130 (Q130P) in the HIM of the K12 protein. The mutation was excluded from 50 normal, unaffected individuals by restriction enyzme analysis and was therefore unlikely to be a common polymorphism. CONCLUSION: A novel missense mutation in the K12 gene leads to MCD in a German kindred. Missense mutations have now been identified within the region encoding the helix initiation motif of the K12 protein in eight of 11 MCD kindreds analysed at the molecular level.

Bilateral severe keratomalacia after acute pancreatitis.

A rare bilateral severe keratomalacia occurred in an emaciated alcoholic, 57-year-old white man with acute necrotic pancreatitis. The patient had a 10-year history of chronic alcoholism. Laboratory and clinical findings were consistent with the diagnosis of a fat malabsorptive and malnutrition syndrome secondary to chronic and acute alcoholic pancreatitis. Visual acuity of both eyes was limited to light perception. Bilateral corneal necrosis after acute pancreatitis has not previously been reported.

Functional anatomy of human lacrimal duct epithelium.

Resorption of tear fluid in the lacrimal ducts has hitherto been controversial; one reason for this has been insufficient knowledge of the anatomical structure and function of the lacrimal duct epithelium. The present study analyzes the structure of lacrimal duct epithelium by means of histological, histochemical, immunohistochemical and electronmicroscopical methods and draws a conclusion about its physiological function regarding its role in immunodeficiency. Investigations were performed on 31 lacrimal systems of 17 male and 14 female individuals (aged 54-88 years). Lacrimal ducts are surrounded by a wide-ranging cavernous system, which is embedded in an osseous canal between the maxilla and the lacrimal bone. The internal wall of the lacrimal canaliculi is lined by a stratified epithelium. The lacrimal sac and nasolacrimal duct contain a double-layered epithelium, which rests on a broad basement membrane. In their apical part epithelial cells contain large lipid droplets and secretory vacuoles. Epithelial cells are faced by microvilli and some tufts of kinociliae are also visible. Goblet cells are integrated in the epithelium as solitary cells or in a characteristic arrangement of several cells. The secretory product of these cells contains carbohydrates including fucose and sialic acid. Inside the surrounding cavernous system serous glands are found that open their excretory ducts into the lacrimal sac and nasolacrimal duct. Some T- and B-lymphocytes and macrophages may be demonstrated immunohistochemically in the submucosa partly penetrating the epithelium. Synthesized mucins of goblet cells form a specialized protective layer on the epithelium of the lacrimal ducts, which functionally serves for a simplified drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells, the protective layer plays a role in antigen defense and prevents invasion of pathogenic agents. The facing of epithelial cells by microvilli gives hints of re-absorption of lacrimal fluid inside the lacrimal ducts.

Tierexperimentelle untersuchungen zur rolle von entzündungsmediatoren bei der hornhautneovaskularisation.

Experimental investigations concerning the role of inflammatory compounds in corneal neovascularization.Natural and synthetic inflammatory compounds were implanted in the corneas of rabbits to clarify the question whether corneal neovascularization is induced by stromal edema alone, or by neovascular mediators. It could be demonstrated that prostaglandin E1 and E2 have an angiogenetic capacity, whereas their precursor (arachidonic acid) as well as PGA1, A2, B2, I2 and Thromboxan A2 were inactive in this regard.Histology showed that corneal neovascularization is always accompanied by the invasion of polymorphonuclear leukocytes. Corneal edema in the beginning of vascularization can be explained by the activities of PGE (vasodilation, increase of vascular permeability, liberation of histamine). The implantation of lipoxygenase-dependent arachidonic acid compounds (5-HETE, Leukotriene B4) demonstrated that these mediators share in the process of neovascularization by inducing the chemotaxis. The above mentioned activities of prostaglandins and leukotrienes could also be demonstrated following penetrating keratoplasty and alkali burns of the anterior segment inducing extensive corneal neovascularization. An analysis of the prostaglandin- and leukotriendependent mechanisms could be achieved by selective PG- and LT- inhibitors. Radioimmunoassays showed a definite correlation between the concentrations of PGE and the amount of neovascularization following alkali burns. The results of our research lead to the following scheme of pathophysiology of corneal neovascularization: hypoxic, chemical, thermic and mechanical alterations of the cornea induce an activation of corneal cytomembranes, thus initiating (1) the cyclooxygenase-dependent synthesis of prostaglandins with consecutive vasodilation and increase of vascular permeability as well as histamine liberation resulting in corneal edema; on the other hand, prostaglandins proved to have a minimal chemotactic activity; (2) the lipoxygenase-dependent synthesis of leukotrienes inducing chemotaxis and diapedesis of polymorphonuclear leukocytes into the corneal stroma. These inflammatory cells are then the main source of newly synthesized leukotrienes maintaining the chemotaxis, and prostaglandins with angiogenetic activity. Cyclooxygenase- and lipoxygenase- inhibitors can inhibit these activities at two different levels, leading to an approach of successful therapy of corneal dieases inducing neovascularization.

[Morphological and metric aberrations of the hand-bones in patients with mongolism--an x-ray study (author's transl)]. / Morphologische und metrische Abweichungen der Handknochen beim Down-Syndrom--eine radiologische Studie.

The evaluation of 2758 X-rays of the hands of 1047 patients with mongolism showed some morphological and metric aberrations: We discovered pseudoepiphyses in 82,4%, a brachymesophalangia in 67%, a dysmesophalangia in 4,6% and clinodactyly in 56,4%. The length of the hands of the patients with mongolism is in all ages shorter than in controls; there is also a distinct acromicria. These alterations are interpreted as a sign of the cerebral affection as well as a general aberration of the mesenchyma.

Orbital involvement in Wegener's granulomatosis.

Orbital granulomas may complicate the course of Wegener's granulomatosis (WG). Granulomas that grow and compress the optic nerve may lead to blindness. Careful magnetic resonance imaging (MRI) is recommended for early detection and follow-up of intraorbital granulomas. Sufficient systemic immunosuppressive treatment should be given as usual for Wegener's granulomatosis. In order to preserve vision orbital decompression may be necessary in rapidly progressive pseudotumor of the orbit.

[Mechanism of the formation of orbital floor fractures. Holographic interferometry studies]. / Zum Entstehungsmechanismus von Orbitabodenfrakturen. Interferenzholographische Untersuchungen.

To date, it has not been possible to answer the question of whether in the classic blow-out fracture the orbital floor is fractured by hydraulic force exerted by the orbital contents or by force transmission within the bony structures of the skull. The aim of our investigation was therefore to reveal the nature of orbital deformation mediated solely by the bone. In holographic interferometry the holographic image of the unstrained object is superimposed on the image of the same object after deformation. The resulting image of the object contains a pattern of interference lines representing the extent of the deformation. This image can be visualized on a TV screen after digital processing of a picture registered by a video camera. This method was used to analyze the deformation of the bony orbit by contact force applied to several points along the orbital rim (each application consisting of 1 N) and by strain distributed evenly upon the orbital rim of the human skull. In all cases maximal deformation occurred in the medial part of the orbital floor no matter where the stress was applied. This finding coincides with the fact that the majority of clinically diagnosed fractures are found in this area. In conclusion, force transmission within the bone is considered as being one determining factor for occurrence of orbital floor fractures.

[Functional results after implantation of Array type refractive multifocal intraocular lenses]. / Funktionelle Ergebnisse nach Implantation von refraktiven multifokalen Intraokularlinsen vom Typ ARRAY.

A prospective study is under way to assess the performance of refractive multifocal intraocular lenses (IOL) of the "Array" type. The results obtained in 35 patients who have been followed up for at least 3 months are reported. In the course of the study it is planned that 100 IOL of this type be implanted. The following parameters were evaluated: distance visual acuity, near visual acuity (Nieden, Jaeger), contrast sensitivity (Regan charts 96%, 50%, 25%, 11%), glare (Brightness Acuity Tester, BAT) for distance and near visual acuity, and other Regan charts. In 28% of the patients the best distance visual acuity was achieved without any correction, while 13% (Nieden 1-3) and 47% (Jaeger 1-3) did not need any correction for their best close visual acuity. Overall, an average correction of +2.6 D was necessary for best near-visual acuity. The average uncorrected distance visual acuity was 0.7, and the average best corrected distance visual acuity was 1.0. In contrast sensitivity testing with the 50% Regan chart, visual acuity decreased by an average of 16% compared with the 96% chart. Even lower contrast reduced visual acuity by 33% (25% chart) and 81% (11% chart) compared with the 96% chart. When glare was tested with BAT at the "high" position the average visual acuity against that without BAT decreased by 19% for the 96% chart, by 25% for the 50% chart, by 45% for the 25% chart and by 82% for the 11% chart. The Array-type IOL allows good distance and near visual acuity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Coronal incision as the surgical approach to the orbits]. / Der Bügelschnitt als chirurgischer Zugang zur Orbita.

The coronal incision of the skin extends from the ipsilateral preauricular region to the other side parallel to the coronal suture. The skin flap can then be mobilized down to nearly the floor of the orbits. We routinely use this incision in the following diseases and surgical procedures of the orbit: (1) osteo- and orbitotomies in premature synostosis of skull bones and craniofacial dysplasias; (2) frontobasal midface traumatology involving the orbit; (3) removal of fronto-ethmoidal mucoceles and tumors with orbital involvement; (4) bilateral medial three-wall and lateral one-wall decompression in Graves' disease; (5) removal of tumors from the upper and medial level of the orbit via a transperiostal incision or an extended supraorbital resection. The major advantages of the coronal incision are the excellent exposure of normal and pathological structures of the (peri-)orbital region and the highly satisfying late cosmetic results.

[Changes in extracellular matrix in the lamina cribosa of patients with secondary glaucoma]. / Veränderungen der Extrazellulärmatrix in der Lamina cribrosa von Patienten mit sekundärem Glaukom.

The aim of this study was to analyze the localization and distribution of extracellular matrix in normal and glaucomatous damaged optic discs using immunohistochemical methods. Five eyes donated for corneal allografting without any history of glaucoma and three other eyes with secondary glaucoma were studied. Immunohistochemical reactions were performed with antibodies against collagen types I, III, IV and VI and against laminin, proliferating antigen KI67 and GFAP. In glaucomatous eyes the characteristic arrangement of collagen fibrils is lacking. Septa of the lamina cribrosa appear enlarged. The immunoreactivity of all examined collagen types is stronger in glaucomatous eyes. The axon basement membranes show an irregular and interrupted pattern. The number of proliferating cells with positive GFAP staining in glaucomatous cribriform plates is distinctly higher. We postulate that fibroblasts and astrocytes in the stroma of glaucomatous lamina cribrosa could be stimulated to increased and uncontrolled proliferation. Associated disorganization and raised secretion of extracellular matrix may lead to axon constriction and, secondarily, to neural degeneration.

[Ophthalmologic symptoms in meningioma of the orbits and in the anterior and medial cranial fossa]. / Ophthalmologische Symptomatik bei Meningeomen in der Orbita und in der vorderen und mittleren Schädelgrube.

UNLABELLED: The records of 182 patients treated for a meningioma of the orbit or the periorbital region between 1971 and 1989 were analyzed. PATIENTS: There were 138 women (76%) and 44 men (24%). Twenty patients had a meningioma of the optic nerve sheath, 78 patients a meningioma involving the sphenoid wing, 29 a meningioma within the sella region, 36 patients a meningioma of the anterior cranial fossa and 19 patients a meningioma of the medial cranial fossa. RESULTS: As an initial symptom 53% complained of decreased vision, 25% of headaches and 16% had exophthalmos. At the first ocular examination visual acuity was decreased below 0.1 in 22%. In 58 eyes we found papilledema and in 60 eyes optic atrophy. Other manifestations were visual field defects, ocular motility deficits in 20%. Histologically the meningiomas were most commonly of the endotheliomatous type (72%). In 23% of the patients, the tumor recurred, which manifested itself in a third by ocular symptoms.

[The efferent lacrimal ducts of the human. Morphological and biochemical studies]. / Die ableitenden Tränenwege des Menschen. Morphologische und biochemische Untersuchungen.

PURPOSE: Infections occur frequently in the region of the efferent tear ducts. Exact knowledge of the anatomical structure and of cellular defense mechanisms is necessary to understand the pathological processes. This study analyzed the efferent tear ducts with regard to physiological function and possible defense mechanism against infections. MATERIALS AND METHODS: We used histological, immunohistochemical and electronmicroscopic techniques to investigate the lacrimal systems from 31 body donors aged 54-88 years. RESULTS: The efferent tear ducts are lined by a double-layered epithelium resting on a broad basement membrane. These cells contain many lipid droplets and secretory vacuoles in their apical part. Inside the epithelium cells are arranged partly in cell groups forming mucous glands, which morphologically resemble goblet cells of the tarsus palpebrae. The secretory products of these cells contain various carbohydrates including sialic acid. Lymphocytes and macrophages are found in the submucosa partly penetrating the epithelium. CONCLUSIONS: Lipids and mucins of epithelial and goblet cells form a specialized protective layer on the epithelium of the tear ducts which enables easy drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells the protective layer prevents invasion of pathogenetic agents.

[HLA typing in high risk keratoplasty]. / HLA-Typisierung bei Risikokeratoplastiken.

UNLABELLED: Improved microsurgical techniques and better immunosuppressive treatment have led to an increase in the number of corneal transplantations. However, graft rejection due to a disparity between donor and recipient major histocompatibility antigens remains the major complication. The risk of graft rejection is further increased in patients with vascularized graft beds and in presensitized persons. Well-designed experimental studies and clinical experience have clearly shown the importance of class-I-antigens. However, class-II antigens have not yet been studied to the same extent. METHODS: Multiorgan donors and corneal graft recipients were HLA typed using the lymphocytotoxicity test previously described by Terasaki. The recipients were typed retrospectively. Cadaver corneal graft donors were typed using a novel HLA typing technique on retinal pigment epithelial cells, as previously described by us. Postoperatively, all recipients were routinely examined for rejection over a period of 2 years. RESULTS: Graft rejection was observed in 25% of the 133 high-risk patients. Of the 13 class-I-typed patients who showed a rejection 9 persons had two or more major histocompatibility mismatches. Of the 12 patients without rejection problems only 5 had two or more HLA class-I-mismatches. Of the patients with one or two matches at the HLA-DR locus there were only 4 out of 9 patients with at least one graft rejection; 5 out of 6 patients showed no signs of rejection. CONCLUSIONS: Mismatches at either class-I- or class-II- gene loci lead to a higher frequency in corneal graft rejection. Apart from the major histocompatibility mismatches, other factors also influence graft rejection, such as the distance between the corneal transplant and corneal vessels, presensitization, and the indication for corneal grafting. If we are to define the factors influencing graft rejection better and further increase our knowledge on the role the major histocompatibility antigens play in corneal graft rejection in a larger patient group, then cooperation with other transplantation centers will be required.

Circular surgical cyclopexy after extensive traumatic cyclodialysis.

The authors operated on a patient who had bilateral ocular hypotony after severe blunt ocular trauma with subsequent circular cyclodialysis and luxation of the lenses. Because of the specific situation, none of the previously reported procedures could be applied. A new surgical technique was used to circularly refixate the ciliary body ab interno. The method described here is simple and can be recommended as an alternative technique to refixate the ciliary body in all aphakic or pseudophakic eyes with persistent ocular hypotony caused by traumatic or surgically induced cyclodialysis.

MRI features of craniofacial fibrous dysplasia.

A 13-year-old female with a 4-year history of monostotic fibrous dysplasia had noticed a progressive proptosis of the right eye and diplopia on upward gaze for 4 weeks. A few years previously an incisional biopsy of the skull had verified the presumed diagnosis of fibrous dysplasia with recurrent bleeding into pathologic cystic bony structures of the skull. The patient was known to have craniofacial fibrous dysplasia with involvement of the frontal and intermediate cranial base, the posterior ethmoidal labyrinth, and the sphenoidal and maxillary sinuses. Eye examination showed a reduced visual acuity in the right eye without defects of the visual field. MR imaging showed a fluid-filled cystic cavity in the orbital frontal bone pushing the globe downwards. Four months later she developed similar symptoms on the other side while proptosis of the right eye was regressive. T2-weighted MRI revealed a large fluid-filled cystic cavity with a fluid-fluid level in the upper part of the left orbit. It is concluded that follow-up studies can be easily performed by MRI without additional exposure to radiation. The total extent of osseous involvement can be determined. Thus, MRI may be helpful in deciding between operative or conservative therapy.